Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis

Hiroshi Umemura, Akira Togawa, Kazuyuki Sogawa, Mamoru Satoh, Kaoru Mogushi, Motoi Nishimura, Kazuyuki Matsushita, Hiroshi Tanaka, Hirotaka Takizawa, Yoshio Kodera, Fumio Nomura

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.

Original languageEnglish
Pages (from-to)577-585
Number of pages9
JournalJournal of Gastroenterology
Volume46
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Fingerprint

High Molecular Weight Kininogens
Proteome
Stomach Neoplasms
Area Under Curve
Peptides
Serum
Tumor Biomarkers
Mass Spectrometry
Kininogens
Carcinoembryonic Antigen
Differentiation Antigens
Neoplasm Antigens
Early Detection of Cancer
ROC Curve
Lasers
Peptide Hydrolases
Up-Regulation
Biomarkers
Carbohydrates
Antigens

Keywords

  • Gastric adenocarcinoma
  • High molecular weight kininogen
  • MALDI-TOF MS
  • Proteomics
  • Serum biomarkers

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis. / Umemura, Hiroshi; Togawa, Akira; Sogawa, Kazuyuki; Satoh, Mamoru; Mogushi, Kaoru; Nishimura, Motoi; Matsushita, Kazuyuki; Tanaka, Hiroshi; Takizawa, Hirotaka; Kodera, Yoshio; Nomura, Fumio.

In: Journal of Gastroenterology, Vol. 46, No. 5, 05.2011, p. 577-585.

Research output: Contribution to journalArticle

Umemura, H, Togawa, A, Sogawa, K, Satoh, M, Mogushi, K, Nishimura, M, Matsushita, K, Tanaka, H, Takizawa, H, Kodera, Y & Nomura, F 2011, 'Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis', Journal of Gastroenterology, vol. 46, no. 5, pp. 577-585. https://doi.org/10.1007/s00535-010-0369-3
Umemura, Hiroshi ; Togawa, Akira ; Sogawa, Kazuyuki ; Satoh, Mamoru ; Mogushi, Kaoru ; Nishimura, Motoi ; Matsushita, Kazuyuki ; Tanaka, Hiroshi ; Takizawa, Hirotaka ; Kodera, Yoshio ; Nomura, Fumio. / Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis. In: Journal of Gastroenterology. 2011 ; Vol. 46, No. 5. pp. 577-585.
@article{4888709e806040cd9d5bc4b932badf45,
title = "Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis",
abstract = "Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.",
keywords = "Gastric adenocarcinoma, High molecular weight kininogen, MALDI-TOF MS, Proteomics, Serum biomarkers",
author = "Hiroshi Umemura and Akira Togawa and Kazuyuki Sogawa and Mamoru Satoh and Kaoru Mogushi and Motoi Nishimura and Kazuyuki Matsushita and Hiroshi Tanaka and Hirotaka Takizawa and Yoshio Kodera and Fumio Nomura",
year = "2011",
month = "5",
doi = "10.1007/s00535-010-0369-3",
language = "English",
volume = "46",
pages = "577--585",
journal = "Journal of Gastroenterology",
issn = "0944-1174",
publisher = "Springer Japan",
number = "5",

}

TY - JOUR

T1 - Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis

AU - Umemura, Hiroshi

AU - Togawa, Akira

AU - Sogawa, Kazuyuki

AU - Satoh, Mamoru

AU - Mogushi, Kaoru

AU - Nishimura, Motoi

AU - Matsushita, Kazuyuki

AU - Tanaka, Hiroshi

AU - Takizawa, Hirotaka

AU - Kodera, Yoshio

AU - Nomura, Fumio

PY - 2011/5

Y1 - 2011/5

N2 - Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.

AB - Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.

KW - Gastric adenocarcinoma

KW - High molecular weight kininogen

KW - MALDI-TOF MS

KW - Proteomics

KW - Serum biomarkers

UR - http://www.scopus.com/inward/record.url?scp=79958766040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958766040&partnerID=8YFLogxK

U2 - 10.1007/s00535-010-0369-3

DO - 10.1007/s00535-010-0369-3

M3 - Article

C2 - 21298293

AN - SCOPUS:79958766040

VL - 46

SP - 577

EP - 585

JO - Journal of Gastroenterology

JF - Journal of Gastroenterology

SN - 0944-1174

IS - 5

ER -